Tazobactam is chemically known as 2α-methyl-2β-(1,2,3-triazol-1-yl)-methylpenam-3α-carboxylate-1,1-dioxide. It is an orally effective pencillin antibiotic having a broad spectrum of antibacterial activity against both gram positive and gram-negative organisms and is disclosed in U.S. Pat. No. 4,562,073.
U.S. Pat. No. 4,562,073 discloses tazobactam of formula (I) and its derivatives. This patent also describes process for their preparation as shown in scheme-1 below:
wherein R1 is hydrogen or trialkylsilyl; R2 is hydrogen, trialkylsilyl or COOR2′ wherein R2′ is hydrogen, C1-18 alkyl, C2-7 alkoxymethyl etc., R3 has the same meaning as above R2′ and R4 represents carboxyl protecting group.
Ogawa et.al Japan. Kokai Tokkyo Koho (1988), 8 pp; JP 63066187) reported the isomer impurity of tazobactam of the formula (V)

Tazobactam, containing the above isomeric impurity around 15-22%, needs to be purified to the level of <0.5%, more specifically <0.2% or <0.1%. The diastereomeric sulfide (VI), formed along with the sulfide of the formula (VII) (Tazobactam intermediate) during the condensation of the 3-halocepham of
the formula (VIII) with 1,2,3-1H-triazole, gets converted to the corresponding isomeric impurity of the formula (V), by the subsequent oxidation followed by deprotection. As a result, Tazobactam isolated from the reaction mixture gets contaminated with the isomeric impurity, the removal of which has been found to be very difficult.
During our research efforts to produce pure tazobactam, we have investigated various methods to remove the isomeric impurity and found that this impurity can be removed at the last stage or at the penultimate stage with certain selected solvents and reagents.
In addition, we also found that tazobactam can be selectively crystallized from the solution containing the above impure tazobactam, if the crystallization is carried out in the presence of certain selected solvents.